Effects of prostaglandin E2 and F2α on the skeleton of osteopenic ovariectomized rats

This article contains the histomorphometric evaluation of the effects of prostaglandin F2α (PGF2α on cancellous bone from the lumbar vertebra and cortical bone from the tibial shaft of ovariectomized, osteopenic rats. These effects were then compared with those of prostaglandin E2 (PGE2). Three-month-old rats were either ovariectomized (ovx) or shamovx. Then, either PGF2α or PGE2 in doses of 1 and 3 mg/kg/day was given subcutaneously for 21 days at 150 days post ovx. Histomorphometric analysis was performed separately on both the primary and secondary spongiosae of the fourth lumbar vertebral bodies (LVB) and on tibial shafts. The ovx rats exhibited osteopenia in both primary (−23% to −37%) and secondary (−20%) spongiosae of the LVB, but not in the tibial shafts at 150 and 171 days post ovx. In the LVB, PGE2 in doses of 1 or 3 mg/kg/day for 21 days restored trabecular bone volume to the levels of sham-ovx controls in the primary spongiosa. However, in the secondary spongiosa, the treatments only thickened the trabeculae. The effects of the PGF2α treatment were similar to those of the PGE2 in both the primary and the secondary spongiosae. While both PGF2α and PGE2 treatments stimulated bone formation in the LVB as indicated by the increases in labeled perimeter, tissue and bone area-based bone formation rates, PGE2 is about 10 times more potent than PGF2α in these effects. The PGE2 treatment also elevated activation frequency in the LVB, while the PGF2α treatment did not. The treatments differed in that PGE2 at these dose levels did not alter the eroded surface in the LVB while PGF2α decreased it significantly. Thus, the increase of the ratio of labeled to eroded perimeter in the LVB in PGF2α treated animals was much more than that in PGE2-treated animals. In the tibial shafts, PGE2 in doses of I and 3 mg/kg/day produced new marrow trabeculae in 2 of 6 and 3 of 6 of the ovx rats. However, no new trabecula was found in PGF2α treated tibial shafts. Higher doses of PGE2 also increased periosteal labeled perimeter, MAR, and BFR/BS, while PGF2α did not produce any significant change in these parameters. Both PGE2 and PGF2α in doses of 1 and 3 mg/kg/day increased the labeled perimeter, MAR and BFR/BS and decreased the eroded perimeter in the endocortical surface. We concluded that both PGF2α and PGEE2 in doses of 1 and 3 mg/kg/day for 21 days exhibited anabolic bone effects. The effects were mostly confined to an increase in trabecular volume in the primary spongiosa of the LVB and in the endocortical surface of tibial shafts. The tissue level mechanism behind this appears to be that PGEE2 and PGF2α can both stimulate osteoblast recruitment and activity. Overall, we found PGE2 to be more potent than PGF2α at the same dose level at the endocortical surface. Furthermore, new marrow trabecular bone formed only after PGE2 treatment. PGF2α differed from PGE2 by significantly reducing the trabecular eroded surface in ovx rats.